Antagonism of the α4 integrin subunit attenuates the acute inflammatory response to stent implantation yet is insufficient to prevent late intimal formation

Journal of Leukocyte Biology

Xiaoli Ma¹  Edward R. O’Brien¹ 

[1] Vascular Biology Laboratory, Division of Cardiology, University of Ottawa Heart Institute, Ontario, CanadaVascular Biology Laboratory, Division of Cardiology, University of Ottawa Heart Institute, Ontario, CanadaVascular Biology Laboratory, Division of Cardiology, University of Ottawa Heart Institute, Ontario, Canada

关键词: restenosis;    leukocyte;    adhesion;   

DOI  :  10.1189/jlb.1203618

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Mononuclear leukocytes infiltrate the artery wall via integrin-mediated mechanisms and play an integral role in intimal formation after stenting. We sought to determine if acute antagonism of the α4 subunit of very late antigen-4 is sufficient for the late attenuation of stent intimal area (IA). Twenty-four hypercholesterolemic rabbits underwent iliac artery balloon injury, followed 2 weeks later by stent implantation, and the animals were randomized to receive an anti-α4 antibody (HP1/2) or a nonspecific isotypic control immunoglobulin (1E6) intravenously 1 h before stenting. Compared with controls, HP1/2-treated rabbits showed 50%, 51%, and 44% reductions in the percentage on intimal cells that were macrophages on days 3, 7, and 28 after stenting and a 59% reduction in intimal proliferation on day 3. Although stent IA was reduced by 63% and 48% in the antibody-treated group compared with the control group on days 3 and 7, this difference was not present on day 28. These data highlight the need for sustained, anti-inflammatory therapies for the prevention of stent intimal formation.

【 授权许可】

Unknown